H. pylori causes gastritis and can contribute to recurrent peptic ulceration. However, investigations have shown that family members can express different manifestations of gastric disease even though they are infected with genetically identical strains of H. pylori. This and other evidence suggest that virulence factors of H. pylori interact with other elements within the gastric milieu to cause the more severe sequelae observed in a subset of infected patients. The immune system is one element that can contribute to the pathogenesis and prevention of disease associated with H. pylori infection. Control of the local immune response to luminal flora depends on the balance of helper T cell subsets. Helper T cells are implicated in the pathogenesis of gastritis and peptic ulceration since, during infection, gastric T cells are markedly increased in numbers and skewed toward a Th1 phenotype and cell-mediated immune responses. Moreover, patients receiving T cell-derived cytokines as immunotherapy can develop gastric ulceration. H. pylori is relatively non-invasive so T cells enhancing cell-mediated immune responses may promote inflammation and, in susceptible individuals, contribute to epithelial damage. This leads to our hypothesis that a relative imbalance in helper T cell subsets favors the stimulation of inflammation and epithelial damage in response to persistent infection with H. pylori. More specifically, Th1 responses increase during natural infection and contribute to epithelial damage, while Th2 cells will favor tissue integrity and immunity. The following specific aims will be addressed to test the hypothesis: 1) characterize the helper T cell subsets which develop in response to H. pylori, 2) elucidate the mechanisms of epithelial damage by Th1 cells, 3) compare the differential effects of Th1 and Th2 cells on the function of gastric epithelium, and 4) characterize the expression of IL-10 receptors on gastric epithelium. In summary, this proposal addresses unanswered questions regarding the molecular basis for the gastric T cell response and defines the mechanisms by which an imbalance in helper T cells modulates inflammation and epithelial damage.